PD-L1 a possible immunotherapy target in mesothelioma

Approximately 20% of patients with malignant pleural mesothelioma have cancer cells that express a protein called programmed cell-death ligand 1 (PD-L1), which is associated with poorer outcomes, according to research presented at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain.

The results suggest this population of patients could be treated with targeted therapies to PD-L1, researchers said. The PD-L1 protein, which is part of the PD-1/PD-L1 immune pathway, is active in many different human cancers, where it is involved in suppressing the antitumor immune response and therefore hampering the immune system's ability to attack the cancer.

Treatments that block this pathway are already showing considerable promise in other malignancies, such as melanoma and lung cancer, leading researchers to question whether this same pathway could be active in malignant pleural mesothelioma.

"We report that PD-L1 is expressed in 20% of malignant pleural mesothelioma patients and is associated with poor outcome, which suggests that this pathway could be targeted with PD-1/PD-L1 inhibitors," said study author Dr. Susana Cedres, from Vall d'Hebron Institute Oncology, Barcelona, Spain.

Researchers analyzed tissue samples from 119 patients with malignant pleural mesothelioma using an anti-PD-L1 stain. PD-L1 expression intensity was scored on a scale of 0 to 3, with 0 signifying no expression; 1, weak expression; 2, moderate; and 3, strong. Then, the scores were compared with survival data and outcomes from those patients.

They found that overall, 20.7% of patients were positive for PD-L1 expression: 18.7% of these showed strong expression of PD-L1, 25% showed moderate expression, while 56.2% showed only weak expression of PD-L1.

Most importantly, patients who were negative for PD-L1 expression survived approximately 11 months longer than patients who were positive for PD-L1 expression (median survival 4.79 vs 16.3 months).

Factors such as gender, smoking, asbestos exposure, and disease stage did not have an effect on whether patient's disease was positive for PD-L1 expression, but researchers did find that expression of the protein was more common in nonepithelial tumors compared with epithelial tumors.

"The results of our study could offer new treatment to this population of patients, identifying a subset of malignant pleural mesothelioma who expressed PD-L1 and could be treated with targeted therapies to PD-L1," Cedres said.